2012 Grants - Abisambra

2012 New Investigator Research Grant to Promote Diversity

Living cells contain compartments, known as the endoplasmic reticulum (ER), used for the synthesis, assembly and folding of proteins. The function of the ER is carefully regulated so that the production of proteins matches the cell's needs and that the proteins are correctly assembled. In situations in which the cell is stressed, such as Alzheimer's disease, the cell activates a stress response that alters the function of the ER.

Tau is a protein strongly implicated in the Alzheimer's disease process. Tau normally functions to help maintain cell structure and transport nutrients. In Alzheimer's disease, tau becomes abnormal and forms neurofibrillary tangles, one of the characteristic features of the disease. Recently, it has been shown that abnormal tau activates the ER stress response in the early stages of Alzheimer's disease.

Jose F. Abisambra, Ph.D. and colleagues have proposed to study how tau activates the ER stress response. They plan to focus on a component of the stress response that inhibits the initiation of protein synthesis. The researchers will study how abnormal tau activates an enzyme called PERK, which regulates the initiation of protein synthesis. They will also measure how abnormal tau affects the rate of protein synthesis by the ER. These studies may identify a key step in the early stages of Alzheimer's disease, and they may provide insights into targets for future drug therapies to alleviate the detrimental effects of abnormal tau.